Lecture 18. Appropriate Cell Differentiation and Stem Cells Flashcards
What is important for appropriate cell differentiation ?
Time and space
How is the progressive nature of development reflected ?
Cells become more and more in their fate until eventually a single fate has become irreversibly determined
When is the fate of a cell determined ?
When it can no longer respond to changing environmental signals and change its differentiation pathway
What is specification ?
The first stage of commitment of cell fate. At this stage cell commitment is still capable of being reversed. The cell has received information but can still be further influenced by new information
What is determination ?
The information received by a cell has fixed its fate and will allow no further change
What can lateral inhibition generate ?
Spacing patterns
What is lateral inhibition ?
A means of ensuring that all cells in a field do not undergo the same differentiation pathway, at the same time
Give an example of a use of lateral inhibition ?
Used to space out the differentiation neurons in the developing nervous system
In embryos, what is lateral inhibition often the result of ?
Differentiating cells producing an inhibitory molecule that acts locally to prevent neighbouring cell differentiating the same way
How does lateral inhibition work in the delta-notch pathway ?
Spaces out the differentiation of neurons in the developing nervous system in time and space
What is the pathway that decides how the cell decides to become a neuron ?
Delta notch
How does a cell decide to become a neuron or not?
- Contiguous neural plate cells express neurogenin, delta and notch.
- With time, one cell expresses more delta into a neuroblast and inhibits the neighboring cells from following a neural fate
What technique have developmental biologists developed to be able to trace cells over time ?
Cell lineage analysis
What is cell lineage analysis needed for ?
Cell fate mapping
What is the concept of cell lineage analysis ?
A method to physically mark a cell early in development and observe it and its descendent cells at a later time
What has cell lineage tracing in the chick been used for ?
Used to map the migration pathway and fate of neural crest cells
Who pioneered cell lineage analysis ?
Nicole M. Le Douarin
What is the genetic tag used in cell lineage analysis ?
Green fluorescent protein
How is a genetic tag used in cell lineage analysis ?
Use of a transgene inserting the gene encoding the GFP protein into specific location of the DNA
Where does GFP come from ?
Jellyfish
What is a brainbow ?
Transgenes tracing individual cells and descendants in developing brain of transgenic mice
What is the purpose of mouse blastocyst being marked with unique colours ?
Follow them over time to demonstrate clonal origins of cells
What is the function of positional information ?
Creating a spatial pattern of cell differentiation
How could a pattern emerge in the embryo cells ?
By receiving a positional address through a set of molecular signals unique to that position
How do cells receive positional information ?
- Localisation of cytoplasmic determinants
- Induction
- Gradients of signals
- Role of physical environment
What is the function of localisation of cytoplasmic determinants ?
A mechanism to make cells different to each other
What is the basis of induction ?
Cell to cell signaling
What is a morphogen ?
A signal involved in pattern formation where cells have a graded response depending on the level of the signal they are exposed to
What is the french flag model used to explain ?
The concept of a morphogen - generation of positional information over a field of cells
Does the french flag model actually exist ?
No
What are some examples of morphogens ?
- Bicoid in drosphilia
2. C. Elegans vulval development
What does drosphilia development show the importance of ?
- Cytoplasmic determinants
- Morphogens
- Local cell signaling
What are maternal effect genes ?
Products of maternal genes - places in the egg by the mother as the egg is maturing - localised within the egg so bicoid gene product localised to one side
What do the products of maternal effect genes work in ?
A concentration dependant manner
What are segmentation genes?
Progressively divide the embryo into segments. Neighboring cells signal to each other through hedgehog and wingless trough mutual signaling to establish the segment boundaries
What are the three groups of genes that act sequentially to establish the body plans ?
- Maternal effect genes
- Segmentation genes
- Homeotic genes
What is positional information ?
The molecular signals and cues experienced by the cells tells them their relative position within the embryo
What is a cue other than cytoplasmic determinants and cell-cell signaling that can be generated ?
Biophysical cues ie. cues by physical environment
What does the effect of biophysical cues do ?
Mechanical signals in bone maintenance and during development
How can physical forces influence cell signaling pathways ?
When embryo’s develop without muscle contractions, the cells of the developing skeleton do not differentiate correctly and gene expression is changed
What did Englers show ?
Stem cells grown in culture on different substrates have different stiffness. Differentiated as neuron on soft substrates and bone cell on stiff substrates
What is the hippo known to act as ?
A sensor of cells/environment
In the hippo pathway what happens when cell proliferation occurs ?
- Hpo an Lat 1/2 are unphosphorylated
2. Yap/Taz can enter the nucleus and gene expression is turned on
In the hippo pathway, what happens when cell proliferation is interrupted ?
- The pathway is activated, Hpo and Lats 1/2 are phosphorylated
- Yap/Taz are phosphorylated and are unable to enter nucleus and control gene expression
What are yap/taz ?
Transcription factors
What happens if the hippo pathway is disrupted in mice ?
Increases in liver size, which increases cell proliferation
What is the function of yap and taz ?
Sensors and mediators of mechanical inputs
What is hippo pathway involved in ?
Sculpting skeletal shape
When is yap protein elevated in skeleton ?
Regions of the developing humerus where shape changes are occuring
When is localised yap protein lost ?
When no movement and shape is altered
What is cell differentiation achieved through ?
Differential gene expression
What are stem cells ?
Undifferentiated cells that are both self renewing and can give rise to differentiated cells when stimulated
What does stem cell differentiation involve ?
Asymmetric cell division
What can stem cells in bone marrow differentiate into ?
All blood cell types
What has the idea that adult stem cells being tissue specific and restricted in their potential been challenged by ?
The identification of rare adult stem cells that can be induced to contribute to very different tissues that are multipotent
What is the problem with the multipotent cells ?
They are rare and challenging to isolate and work with
Where are embryonic stem cells derived from ?
Inner cell mass of the mammalian blastocyst
What do embryonic stem cells not have ?
No specification of cell fate within the inner cell mass
Where can embryonic stem cell be grown in?
Culture and maintained in an undifferentiated state
What do embryonic stem cells have the capacity to do ?
Give rise to every cell type in the body
What is the objection to using embryonic stem cells ?
Ethical issues
What do stem cells have the potential to treat ?
Neurodegenerative disorders, muscle degeneration, diabetes, spinal cord injuries, blood cell repopulation
What type of cell is embyronic stem cells ?
Pluripotent
What are stem cells that give rise to a more limited number of cell types known as ?
Multipotent
What is an example of multipotent stem cells ?
Hematopoietic stem cells - bone marrow
What are stem cells that give rise to only one type of differentiated cell ?
Unipotent
What is an example of unipotent stem cells ?
Satellite cells in muscle
What is meant by totipotent ?
The zygote, fertilised egg cell- an give rise to a complete new organism
What is induced pluripotent stem cells ?
Adult differentiated cells could be reprogrammed to embryonic stem like cells by introducing the genes for four transcription factors associated with pluripotency
What can organoids be produced from ?
Stem cells
What are organoids ?
Structures that mimic aspects of tissues and organs
